Preparation of methionine hydantoin



United States Patent Oflice 2,717,251

Patented Sept. 6, 1955 of about 73% was obtained with diethylamine, whilst 2,717,252 with tri-n-butylamine, triethanolamine, diethanolamine and isopropylamine, the yields ranged between about 40% PREPARATION OF METHIONINE HYDANTOIN and 50%. In the case of tri-n-butylamine being used the David Oliver Holland Dorking England assignor to Beecham Research iaboratories Limited: Betchworth, msoluble i had almost entirely dlssolvedcarbon dioxide was passed in for 3 hours until the initially England, a company of Great Britain By contrast, substantially no yield was obtained with No Drawing. Application December 15, 1952, 35: :23 S gs? :22:52 lamme of whlch very htfle serial 326168 The hydantoin can be hydrolysed to methionine in high Claims priority, application Great Britain yield by the use of alkaline hydrolysing agents. For the December 21, 1951 preparation of methionine in this way it is not necessary,

10 Claims. (CL 260 309.5) however, to lsolate the hydantoin. After the reaction with carbon dioxide is complete the mixture can be 15 treated with the alkaline hydrolysing agent, the alcohol Thls lhvehtloh 15 an lmphoved Prom?SS the P P and the amine recovered and the hydrolysis can then be non of methioninehydanto n (5-p-methylth1oethy1hydancarried out in any desired manner. The recovery of tom) from methionine mtrile (a-anunoy-methylth amine is very high and it can be used in the alcohol also butyromtnlql recovered for further reaction.

The reaction of methionine nitrile with carbon dioxide I claim: at Ordinary telllpfil'tlthfe ill the absqnce of atfxlhary 1. Process for preparing methionine hydantoin by reagent or cataly st 1s very slow and yields methiomne hyacting methionine nitrile i carbon dioxide in the dahtohl as a mlhor Product h Th1s method has been presence of an amine of basicity substantially greater than descnbed by Bucherer and Steiner in J. Prakt. Chem., vol. the nitrile" PP- Object of the P 2. Process as claimed in claim 1 in which the carbon ventlfm 18 to Improve thls l'eactloh so that good Ylelds of dioxide is passed through an aqueous alcoholic solution methionine hydantoin will be obtalnable. f the nitrile and amine According to the ihvhntloh methlomhe Hittite 3. Process according to claim 1 in which the amine is a acted with carbon dioxide in the presence of an atmne of lower 1 1 basicity substantially greater than the nitrile. The amine 4 process according to claim 1 in which the amine is P Y 156d in the P QPQ of at least one mole is of the group consisting of triethylamine, trimethylamine of amine per mole of the mtnle. and diethylamine.

The amillfl y be P y, secondary P lflh 5. Process according to claim 1 in which the amine is is preferably of the lower aliphatic series comprising an 1k 1 i alkylamines, alkanolamines and alkylalkanolamines. The 3 process according to 1 1 1 i hi h th a i i preferred amine is triethylamine. an alkylalkanolamine.

Methionine hydantoin y be hydrolysed to give meth" 7. Process according to claim 1 in which the amine is ionine which is well known to be a vital factor in human h 1 i h and an u nutrltlon- Methlohlfle has a valuable 8. Process according to claim 1 in which there is used therapeutic action in the case, for example, of certain liver 40 at least one l f h amine per l of the nitrile diseases. 9. Process for preparing methionine hydantoin by pass- The lhvehtlon 1S Illustrated 111 the followlng example! ing carbon dioxide through an aqueous alcoholic solution Carbon dioxide was bubbled for one hour through a f methionine nitrile and triethylamine solution of 6.5 g. (0.05 mole) of pure methionin nitrile 10. Process according to claim 9 in which at least one 111 50 Of 50% aqueous alcohol to which mole of mole of triethylamine per mole of methionine nitrile is triethylamine had been added. After standing overnight d I (or for some hours) at ordinary temperature the mixture was concentrated under reduced pressure to remove alcohol arid made strongly acid with concentrated hydrochloric acid, whereupon the hydantoin separated. After References Cited in the file of this patent UNITED STATES PATENTS standingin a refrigerator for some hours the hydantoin 2,409,754 Henze Oct. 22, 1946 was collected and washed with a little cold water, the 2,557,913 Livak et al June 19, 1951 filtrate and washings being concentrated to yield a second 2,642,459 White .Q June 16, 1953 crop of the hydantoin. The yield of hydantoin was 90% of the theoretical. When, instead of triethylamine, the OTHER REFERENCES equivalent amount (0.05 mole) of trimethylamine or 13- Ware, Chem. Reviews, vol. 46, pp. 422-25 (1950). diethylaminoethanol was used, slightly lower (about Bucherer et-aL, I. Prakt. Chem., vol. 140, pp. 291-316 yields of the hydantoin were obtained. A yield (1934). 

1. PROCESS FOR PREPARING METHIONINE HYDANTOIN BY REACTING METHIONINE NITRILE WITH CARBON DIOXIDE IN THE PRESENCE OF AN AMINE OF BASICITY SUBSTANTIALLY GREATER THAN THE NITRILE. 